Vascular diseases represent a principal cause of morbidity and mortality in modern human societies. While cardiovascular and cerebrovascular disorders, such as congestive heart failure and the catastrophic events of myocardial infarction, sudden cardiac death or stroke, are widely recognised, vascular dysfunction may as well obstruct blood supply to other organs or body parts, such as for example intestines, kidneys, upper or lower extremities (e.g., peripheral artery occlusive disease).
A central etiologic component of vascular diseases is atherogenesis, i.e., the progressive formation of atheromatous plaques in subintimal layer, which instigates inflammatory atherosclerotic lesions within arteries and arterioles. Plaque deposition may lead to arterial stenosis, causing inadequate blood supply to organs fed by the artery. More often, inflammation of the plaque may contribute to rupture of the fibrous cap resulting in thrombus formation and ensuing infarction.
Predisposition for, incidence and/or rate of progression of vascular pathogenic alterations, including inter alia endothelial dysfunction, increased vascular permeability, increased leukocyte and platelet aggregation and eventually atherogenesis and atherosclerosis, may be augmented in or associated with various risk factors or disease conditions, such as, among others, with acute and chronic inflammatory states and diseases, and with chronic vascular challenges. For instance, patients with chronic inflammatory disorders such as rheumatoid arthritis and systemic lupus erythematosus can suffer from accelerated atherogenesis (Solomon et al. 2003. Circulation 107: 1303-7; Roman et al. 2003. N Engl J Med 349: 2399-406); elevated levels of endotoxin in human bloodstream have been associated with an increased risk of atherosclerosis (Stoll et al. 2004. Arterioscler Thromb Vasc Biol 24: 2227-36); and repeated administration of endotoxin has been shown to increase atherosclerotic lesion formation in rabbits on a hypercholesterolemic diet (Lehr et al. 2001. Circulation 104: 914-20); and even single inflammatory challenges such as vaccination, infusion of C-reactive protein, or endotoxin administration may cause endothelial dysfunction in humans.
Consequently, there exists an urgent need for diagnostic tools capable of detecting the vulnerability of the vessel wall towards atherogenic stimuli, particularly in subjects and patient groups that may be at risk for developing vascular alterations or are suspected or known to suffer from vascular pathology. Moreover, there also exists a need for novel targets which allow for increasing the protective capacity of the vessel wall against atherogenic stimuli, thereby providing for further therapeutic and preventative measures.